An estimated two million people a year are affected by arterial and venous thrombosis. Treatment with thrombolytic drugs is effective, but current procedures are only successful in dissolving thrombi in 70% to 80% of the patients. EKOS has developed an ultrasound catheter device and demonstrated an enhanced thrombolytic effect in-vitro and in vivo. The ultrasound transducer design and the associated acoustic parameters have been improved and early in vivo results indicate that ultrasound facilitated thrombolysis is as effective or better than the current standard-of-care pulse-spray type of devices for delivery of thrombolytic agents. The specific aims are: 1. Continue study of acoustic mechanisms. Specific tasks include: 1) study the role of microbubbles in enhancing thrombolysis with ultrasound; 2) examine the effect of various source pulsing conditions; and 3) develop an in-vitro blood clot model which simulates flow conditions in a partially occluded blood vessel. 2. In an animal model that simulates arterial thrombus occlusion, compare the safety and efficacy of the ultrasound infusion catheter with a conventional intravascular pulse-spray type infusion catheter. 3. Conduct a 10-patient pilot trial of peripheral arterial thrombolysis using the EKOS device and use the results to plan and initiate a prospective, multi-center study of 40 patients. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE